Characterization of Heat Shock Protein-Specific T Cells in Atherosclerosis

Abstract

A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) V␤ expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein 1␣, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR V␤5.2 family in all lines. These cytokine, chemokine, and V␤ profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients.

Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases

“…In addition, antibody levels to GroEL and human HSP60 were found to be higher in atherosclerosis patients in comparison to periodontitis patients and healthy subjects, and GroEL-specific T-cells were detected in both the circulation and in some atherosclerotic lesions in atherosclerosis patients (Yamazaki et al 2004). In addition, T-cell lines established from atherosclerotic plaques that are specific for GroEL and for human HSP60 have similar cytokine profiles and phenotypic characteristics to P. gingivalisspecific lines from periodontitis patients (Ford et al 2005). These studies support the notion that bacterial HSP can induce immune responses that would be expected to promote inflammation in the atheroma itself.…”

Periodontal Disease and Atherosclerotic Vascular Disease: Does the Evidence Support an Independent Association?

“…106 Moreover, cross-reactive T cells have been found in diseased periodontal tissue, peripheral blood, and atherosclerotic lesions. 107 Studies in experimental animals lend further support to the hypothesis that cross-reactivity of the immune response to bacterial HSP has a role in accelerating atherosclerosis. In murine models, atherosclerosis is augmented by immunization with recombinant HSP.…”

Chronic Infections and Atherosclerosis

“…Further, the high degree of homology between microbial and human HSP60 has led to the concept that molecular mimicry between the microbial and endogenous HSP60 may be involved in the pathogenesis of some autoimmune disease [11][12][13]. In atherogenesis, cellular and humoral immunity against HSP60 derived from infectious pathogens could promote the development of atherosclerosis because the immune systems may recognize endogenous HSP60 expressed on the surface of endothelial cells [14][15][16].…”